PROJECT SUMMARY The Pathology Core is responsible for overseeing the realm of human tissue, which is ultimately the life blood of the translational projects proposed in this DF/HCC Ovarian Spore application. The primary mission of the Pathology Core is to ground the projects in the visual realities of tissue cyto-morphology as the individual project directors explore new therapies and biomarkers of therapeutic response. The first aim of this core is to ensure that the projects are in compliance with IRB-approved protocols. The second aim will be to ensure access to the highest quality tissue. This task is multifaceted and entails close coordination between core investigators and personnel involved in consenting patients, delivering tissues to the Frozen Section room for allocation, and transporting the tissue to the proper destination. In this setting, quality of service pertains to both the condition of the tissue and the precision with which the tissue is analyzed to ensure that the proper cellular components are selected for study. The third aim for this core will be to provide expert histopathologic interpretation when needed and aid in experimental design and execution when tissue is utilized. All of these aims will be executed in the context of each individual project and other cores. In Project 1 the core will be involved in tissue allocation for sequencing, organoid or patient-derived xenograft generation, and paraffin embedding and sectioning. The core will aid in antibody optimization, immunohistochemical staining of tissue sections, and interpretation of results obtained on tissue in the context of multiple clinical trials. In Project 2, involving a vaccine trial, critical tasks will include allocation of fresh tissue for all activities surrounding vaccine generation and organoid generation as well as for generating paraffin embedded sections. The core will help to assess immune response at the tissue level through multi-plex immunofluorescence analysis to help maximize the information that can be gleaned. In Project 3, the core will aid with fresh, frozen, and fixed tissue acquisition and allocation to allow for the varied analyses to be performed in the context of a clinical trial. Moreover, the core investigators must be ever cognizant of maintaining the tissue banks at each site and providing tissue for the Organoid, model organisms, and biomarkers core as well as aiding the biostatistics core in interpretation of immunohistochemical results with respect to patient outcomes. Amidst this panoply of diverse tasks, the core investigators must maintain an organized hierarchy of task assignment and carefully set priorities. This will be achieved by experienced pathologist-investigators who will interact regularly and effectively to integrate the work being done across multiple institutions and develop protocols and procedures with established safeguards of quality assurance. Finally, this integrated Pathology Core will be dynamic, with attention to weaknesses in the data interpretation and consideration of innovative approaches prompted by either necessity or opportunity.